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Sheffield scientist investigates how to stop breast cancer spreading to the bone

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Research identified molecule which plays a critical role in helping secondary breast tumours form in the bone

A leading scientist from the University of Sheffield is investigating a possible key to preventing breast cancer spreading to the bone. The cutting-edge research is funded by a grant worth almost £200,000 by research charity Breast Cancer Now.

If breast cancer spreads around the body – known as secondary breast cancer – it becomes incurable. Over 1,000 women in South Yorkshire are diagnosed with breast cancer every year, and more than 220 women in the region die from the disease each year.

The majority of the 11,500 women who die as a result of breast cancer each year in the UK will have seen their cancer spread. The bone is one of the most common places for breast cancer to spread to, with around 70 per cent of secondary breast cancer patients having tumours in the bone.

With previous funding from Breast Cancer Now, Professor Alison Gartland from the University of Sheffield’s Department of Oncology and Metabolism made a significant discovery – published in the journal Nature – that a molecule called lysyl oxidase (LOX), which is released by primary breast tumours, is responsible for making holes in bones. These holes help prepare or ‘prime’ bone for the arrival of breast cancer cells, increasing the tendency of cancer cells to spread there.

Professor Gartland’s team will now investigate how a second molecule – P2X7R – interacts with LOX to help breast cancer spread, and whether it could be targeted with drugs to stop breast cancer spreading.

“We have since found that P2X7R can work with LOX to prepare the bone environment for the arrival of secondary cancer cells, so this Breast Cancer Now grant will enable us to investigate this further.

“We hope to find out whether drugs that block P2X7R, which have already been shown to be safe in clinical trials for arthritis, could prevent cancer spreading to the bone. This would be of great benefit in the fight against this horrendous disease that has such devastating effects.”

Firstly, the team will study how P2X7R interacts with LOX in individual bone cells, before examining how drugs that block P2X7R modify the effect of LOX on bone tissue. By doing this, the team hopes to establish whether LOX is only able to prime the bones in the presence of P2X7R, and will investigate whether any other molecules are also involved in helping cancer to spread. Next, the research team will test the effects of drugs that block P2X7R and LOX using mouse models of primary and secondary breast cancer.

They will use micro-CT scans to assess the number and size of the holes in bone following this treatment, as well as taking blood samples to measure levels of LOX and other molecules that indicate possible spread to the bone. They will also analyse tumour growth across a variety of metastatic sites, to assess the effects of blocking P2X7R on the formation of secondary tumours.

Dr Richard Berks, Senior Research Communications Officer, Breast Cancer Now, said, “If we are to stop people dying from breast cancer, we must find a way to prevent the disease spreading. Professor Gartland’s research could help uncover which molecules are vital in helping breast cancer spread to the bones, and identify drugs that might stop this happening.”

Breast Cancer Now is the largest breast cancer charity in the UK, dedicated to funding pioneering research into this devastating disease. The charity’s ambition is that, by 2050, everyone who develops breast cancer will live.

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